Liu Lu, Yu Wanli, Cai Kuojun, Ma Siyuan, Wang Yanfeng, Ma Yuhui, Zhao Hongqiong
College of Veterinary Medicine, Xinjiang Agricultural University, Urumqi 830052, Xinjiang, China.
Zhaosu Xiyu Horse Industry Co., Ltd. Zhaosu County 835699, Yili Prefecture, Xinjiang, China.
Heliyon. 2023 Jul 25;9(8):e18623. doi: 10.1016/j.heliyon.2023.e18623. eCollection 2023 Aug.
() is a zoonotic opportunistic pathogen that can cause life-threatening infections. The rapid evolution of multidrug-resistant and the fact that there is no currently licensed effective vaccine against warrant the need for vaccine development. Reverse vaccinology (RV), which involves screening a pathogen's entire genome and proteome using various web-based prediction tools, is considered one of the most effective approaches for identifying vaccine candidates. Here, we performed a pangenome analysis to determine the core proteins of . We then used the RV approach to examine the subcellular localization, host and gut flora homology, antigenicity, transmembrane helices, physicochemical properties, and immunogenicity of the core proteins to select potential vaccine candidates. The vaccine candidates were then subjected to epitope mapping to predict the exposed antigenic epitopes that possess the ability to bind with major histocompatibility complex I/II (MHC I/II) molecules. These vaccine candidates and epitopes will form a library of elements for the development of a polyvalent or universal vaccine against . Sixteen complete proteomes were found to contain 6,238 protein families, and the core proteins consisted of 3,969 protein families (∼63.63% of the pangenome), reflecting a low degree of intraspecies genomic variability. From the pool of core proteins, 483 nonhost homologous membrane and extracellular proteins were screened, and 12 vaccine candidates were finally identified according to their antigenicity, physicochemical properties and other factors. These included four cell wall/membrane/envelope biogenesis proteins; four amino acid transport and metabolism proteins; one cell cycle control, cell division and chromosome partitioning protein; one carbohydrate transport and metabolism protein; one secondary metabolite biosynthesis, transport and catabolism protein; and one defense mechanism protein. All 12 vaccine candidates have an experimentally validated 3D structure available in the protein data bank (PDB). Epitope mapping of the candidates showed that 16 MHC I epitopes and 13 MHC II epitopes with the strongest immunogenicity were exposed on the protein surface, indicating that they could be used to develop a polypeptide vaccine. Thus, we utilized an analytical strategy that combines pangenome analysis and RV to generate a peptide antigen library that simplifies the development of multivalent or universal vaccines against and can be applied to the development of other vaccines.
（某病原体名称）是一种人畜共患的机会性病原体，可导致危及生命的感染。多重耐药性的快速演变以及目前尚无针对该病原体的有效许可疫苗这一事实，使得疫苗研发成为必要。反向疫苗学（RV），即使用各种基于网络的预测工具筛选病原体的整个基因组和蛋白质组，被认为是识别候选疫苗最有效的方法之一。在此，我们进行了全基因组分析以确定该病原体的核心蛋白。然后我们采用RV方法来研究核心蛋白的亚细胞定位、宿主和肠道菌群同源性、抗原性、跨膜螺旋、理化性质及免疫原性，以筛选潜在的候选疫苗。随后对候选疫苗进行表位作图，以预测具有与主要组织相容性复合体I/II（MHC I/II）分子结合能力的暴露抗原表位。这些候选疫苗和表位将构成开发针对该病原体的多价或通用疫苗的元件库。发现16个该病原体的完整蛋白质组包含6238个蛋白质家族，核心蛋白由3969个蛋白质家族组成（约占全基因组的63.63%），反映出种内基因组变异性较低。从核心蛋白库中筛选出483个非宿主同源的膜蛋白和细胞外蛋白，最终根据其抗原性、理化性质及其他因素确定了12个候选疫苗。其中包括4个细胞壁/膜/包膜生物合成蛋白；4个氨基酸转运和代谢蛋白；1个细胞周期调控、细胞分裂和染色体分配蛋白；1个碳水化合物转运和代谢蛋白；1个次级代谢产物生物合成、转运和分解代谢蛋白；以及1个防御机制蛋白。所有12个候选疫苗在蛋白质数据库（PDB）中均有经过实验验证的三维结构。对候选疫苗的表位作图显示，16个MHC I表位和13个免疫原性最强的MHC II表位暴露在蛋白质表面，表明它们可用于开发多肽疫苗。因此，我们利用了一种结合全基因组分析和RV的分析策略来生成一个肽抗原库，该库简化了针对该病原体的多价或通用疫苗的开发，并且可应用于其他疫苗的开发。
